Homeosis refers to a class of mutations which brings about the replacement of one body part with that of another normally found elsewhere on the animal. Molecular analysis of the Drosophila homeotic regulatory genes has shown that the proteins which they encode contain a highly conserved 60 amino acid domain (the homeo domain). Homeo domain containing proteins are part of the mechanism which controls the diversity of body parts in Drosophila. The significance of the homeo domain has been highlighted by the recent demonstration that homeo domain proteins are found in other metazoans, including mice and humans. These observations suggest the exciting possibility that genes which control the insect body plan may have partial homology to functionally related genes which control the body plans of mammals. By identifying the functional roles these genes play in mouse development, we hope to gain insight into the basic principles which govern mammalian development. Initiated in January 1986, the first phase of this project for one of the mouse genes is near completion. Utilizing the nucleic acid sequences that encode a Drosophila homeo domain as a tool, we have cloned and sequenced an homologous mouse gene and its corresponding cDNA. Primary structure comparisons of this mouse homolog to Drosophila homeotic genes and their encoded proteins demonstrates that it shares homology in both gene structure and in the amino acid sequence of the protein. Messenger RNA analysis shows that the gene is expressed early in embryogenesis and in the central nervous system of both newborn and adult mice. This information is now serving as a framework for the construction of expression vectors, synthetic peptides, fusion proteins, antibodies and transgenic mice. These tools will be used to determine the functional role of this protein in mouse development.